Merging two or more liquids to form a solution generally requires some combination of convective and diffusive transport. This is a critical element of many analytical methods. Although blending by convective transport alone can be achieved very quickly, it only provides a macroscopic level of mixing. Efficient mixing within convectively generated microenvironments requires diffusion. Diffusive mixing is most effective when the transport distance is a few microns or less.
Convective transport is a physical process requiring energy. Generally, this energy is provided in the form of mechanical agitation, as in the case of mechanical stirrers or vortex mixers. This direct addition of energy at the point of mixing is perhaps the reason this form of mixing is referred to as "dynamic mixing." Liquids may also be mixed by transport through a bed of particles where eddy diffusion and laminar flow provide the convective mixing element. An external pump or gravity drives convection in this case. This form of mixing is often referred to as "static mixing," possibly because there is no mechanical component at the point of mixing. Actually, any system in which there is convective transport is in a dynamic state of flux. The term static mixing is obviously both a misnomer and a contradiction but will be used herein because of its broad usage in the literature.
Mixing confluent liquid streams is an important, but difficult operation in microfluidic systems. Electroosmotically driven, microfluidic analytical systems in which mixing occurs in channels of 50-100 .mu.m width are known in the art. Such mixing is generally achieved by laterally merging liquid streams in the same plane into a central channel at a T, Y, or + junction, where they mix by lateral diffusion. Channels of this width are too large for rapid diffusive mixing and too small to allow installation of a dynamic mechanical mixer. Some type of static mixer capable of substantial lateral transport would seem to be a better alternative. Because the volume of current microfluidic systems is generally in the range of 1-10 nL/cm and it would be desirable to achieve mixing within 0.1-1 mm of transport distance along a channel, mixing would have to be achieved in a volume of 0.1-2 nL. The question is how to build a static mixer of this volume with a high degree of lateral transport.
Designing a static mixer to solve this problem is facilitated by an analysis of mixing in particle beds. Longitudinal mixing along the flow axis through the bed results from i) laminar flow in the interparticle space, ii) poor mass transfer between stagnant pools of liquid within the particle matrix, and iii) radial differences in the rate of analyte transport. Even higher degrees of mixing can be achieved by using porous particles to increase the volume of stagnant mobile phase and limit mass transfuser further. Because this is a kinetic process, the degree of longitudinal mixing is flow rate dependent. Obviously, longitudinal mixing is most important when there is a longitudinal, or time based variation in the composition of the liquid stream entering the mixer. This is not the case in the microfluidic systems described above. The problem is a spatial difference produced by two, or more streams entering the mixer at different points. This is almost totally an issue of lateral heterogeneity. Lateral mixing is achieved in packed beds by transchannel mixing. As liquid from adjacent streams merges between particles there is both diffusive mixing and some degree of flow heterogeneity arising from packing variations within the bed. Transchannel coupling is very effective in averaging small degrees of lateral heterogeneity within chromatography columns, but does so over the length of many particles and a relatively large volume. The degree of lateral mixing in packed beds is too small to accommodate the substantial lateral heterogeneity encountered in merging two streams in microfluidic systems.
There is therefore a need for a static mixer i) of less than 500 pL total volume, ii) capable of continuously mixing two streams of liquid, and iii) having a high degree of lateral mixing. The present invention is directed toward meeting this need.